Best replaces shoulder-injury victim Jerry Flannery in the starting line-up with Munster front row Frankie Sheahan providing back-up from the bench.
It is the only change to the side that was beaten by Australia during the summer tour.
Best's Ulster colleague and namesake Neil is preferred to Simon Easterby at blindside flanker while Munster lock Donncha O'Callaghan keeps out Malcolm O'Kelly, Ireland's most capped player.
The backline has a familiar look to it with Leinster's Girvan Dempsey edging out Geordan Murphy for the number 15 shirt once again.
Brian O'Driscoll captains the side for the 31st time with Ulster midfielder Paddy Wallace the only uncapped player in the squad.
Ireland head coach Eddie O'Sullivan said: "As usual the back and second rows were the most difficult areas of discussion.
"Other than that it was pretty straightforward so it wasn't the toughest selection meeting we've had.
"But there are quite a few guys on the bench who could have started. In general we've selected on form.
"Girvan Dempsey has been playing well for Leinster and scored a few tries in the Heineken Cup during the opening rounds.
"Geordan has been playing on the wing for Leicester and Girvan just shaded it on form.
"Leaving out Simon Easterby was the most difficult decision. I'm a fan of his. He's always been close to or in the team and it was a very tough call.
"But if you look at form Neil has been playing very well for Ulster. It was a toss of the coin between the two of them."